Myelodysplastic SyndromesPhase 1/2NCT03175978
IGF-MTX Conjugate in the Treatment of Myelodysplastic Syndrome
A Phase 1/2 study testing IGF/MTX in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by IGF Oncology, LLC at 2 sites in United States.
Trial summary
The primary objective of this study is to determine the safety and tolerability of utilizing the insulin-like growth factor-1-methotrexate conjugate, 765IGF-MTX for the treatment of advanced, previously treated myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and oligoblastic acute myelogenous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, With Excess of Blasts
- What is being tested?
- IGF/MTX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Feb 2018to 30 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
- Confirmed histologic diagnosis on bone marrow biopsy and aspirate within 28 days of trial entry prior to starting cycle 1.
- Platelets > 10 x 10^9/L
- ECOG performance status of 0, 1 or 2
- Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; prior use of systemic methotrexate > 1 month prior to study entry is allowed. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion.
- Patient must have recovered from the acute toxic effects (≤ grade 1 CTCAE v.4.0) of previous anti-cancer treatment prior to study enrollment; the only exception is that grade 2 neuropathy is permitted
- Adequate organ function within 14 days of study registration
- Negative serum pregnancy test in females. Male and female patients with reproductive potential must use an approved contraceptive method if appropriate
Who cannot join
- ECOG PS >2.
- Patients with active extramedullary disease.
- Pleural effusions or ascites.
- Grade 3 peripheral neuropathy within 14 days before enrollment.
- Active uncontrolled infection or severe systemic infection (enrollment is possible after control of infection).
- Myocardial infarction within ONE months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
Show all 13Show fewer
- Pregnant or breastfeeding - methotrexate is Pregnancy Category X - has been reported to cause fetal death and/or congenital abnormalities. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 10% in patients with a prior history of diabetes, prior to study enrollment.
- Serious concomitant systemic disorders (e.g., active uncontrolled infection or uncontrolled diabetes) or psychiatric disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
- Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
- Any history of epilepsy or a seizure disorder or any known prior seizures.
- Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IGF or methotrexate.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic
Rochester, Minnesota, 55905
Regions Cancer Care Center
Saint Paul, Minnesota, 55101
About this study
Official title: Pilot Study of IGF-Methotrexate Conjugate in the Treatment of Myelodysplastic Syndrome, CMML and Oligoblastic AML
The primary objective of this study is to determine the safety and tolerability of utilizing the insulin-like growth factor-1-methotrexate conjugate, 765IGF-MTX for the treatment of advanced, previously treated myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and oligoblastic acute myelogenous leukemia (oligoblastic AML or O-AML), including determining the maximum tolerated dose (MTD).
Read the detailed description
This pilot study will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal. Assessment of response will be confirmed by bone marrow studies performed at the end of cycles 2, 4, and 6 (each +/- 3 days).
Pharmacokinetics will be performed before and for up to 24 hours after drug administration on days 1 (for 24 hrs) and 15 (for 24 hrs) of cycle 1. Pharmacodynamic samples will be assessed pre-dosing on day 1 of cycle 1, pre-dosing on days 1 and 15 of cycle 2, and pre-dosing on day 15 of cycles 4 and 6.
- Conditions
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, With Excess of Blasts
- Being tested
- IGF/MTX
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IGF/MTXDrug
Also called insulin-like growth factor-1/methotrexate conjugate, 765IGF-methotrexate
765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
| Study group | Role | What they receive |
|---|---|---|
| IGF/MTX | Experimental | This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal. Receives: Drug: IGF/MTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events
Number of Participants with Treatment-Emergent Adverse Events through study completion, up to a maximum duration of 10 28-day cycles.
Measured: Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.
Secondary outcomes (11)
Response Criteria for AML, Complete Remission (CR)
Bone marrow blasts, platelet count, independence of red cell transfusions. Bone marrow blasts <5%, absence of blasts with Auer rods, absence of extramedullyary disease, absolute neutrophil count >1.0 x 10(9)/L, independence of red cell transfusions.
Measured: Assessed after 2 cycles of 28 days each.
Response Criteria for AML, CR With Incomplete Recovery
All CR criteria except for residual neutropenia (<10(9)/L) or thrombocytopenia (<100x 10(9)/L).
Measured: Assessed after 2 cycles of 28 days each.
Response Criteria for AML, Relapse.
Bone marrow blasts greater the 5% or reappearance of blasts in the blood, or development of extramedullary disease after complete remission or complete remission with incomplete recovery..
Measured: Assessed after 6 cycles of 28 days each.
Response Criteria for MDS, Complete Remission (CR)
Bone marrow less than 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood values of Hgb greater than or equal to 11 d/dL, platelets greater than or equal to 100*10^9 platelets/L, neutrophils greater than or equal to 1.0*10^9 neutrophils/L, blasts equal to 0%.
Measured: Assessed after 6 cycles of 28 days each.
Response Criteria for MDS, Marrow CR
Bone marrow less than or equal to 5% myeloblasts and decreased by greater than 50% over pretreatment.
Measured: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Stable Disease
Failure to achieve at least PR, but no evidence of progression for greater than 8 weeks
Measured: Assessed after 6 cycles of 28 days each. Both patients had at least stable disease for at least 6 cycles.
Response Criteria for MDS, Failure
Death during treatment or disease progression characterized by worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment
Measured: Assessed after 6 cycles of 28 days each.
Response Criteria for MDS, Disease Progression, Blasts Measurements
Absolute blast count.
Measured: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Disease Progression, Hgb
Hemoglobin in g/dL
Measured: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Disease Progression, Neutrophils
Neutrophil count in 10(9)/L
Measured: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Survival, Death
Survival over the full study time period and follow up to 23 months after initiating treatment.
Measured: All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start21 Feb 2018
- Primary completion30 Jun 2021
- Study completion30 Sep 2021
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- IGF Oncology, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mrinal S Patniak, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03175978
- Sponsor's protocol ID
- AML-03
- Status last verified
- May 2024
- First submitted
- 25 May 2017
- Last updated
- 21 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of IGF-Methotrexate Conjugate in the Treatment of Myelodysplastic Syndrome, CMML and Oligoblastic AML
- ClinicalTrials.gov ID
- NCT03175978
- Acronym / sponsor ID
- AML-03
- Conditions
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, With Excess of Blasts
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding
- Enrolment
- 2 participants (actual)
- Lead sponsor
- IGF Oncology, LLCIndustry (pharma, biotech, devices)
- Study start
- 21 Feb 2018 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 5 Jun 2017 (actual)
- Results
- Posted 21 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine the safety and tolerability of utilizing the insulin-like growth factor-1-methotrexate conjugate, 765IGF-MTX for the treatment of advanced, previously treated myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and oligoblastic acute myelogenous leukemia (oligoblastic AML or O-AML), including determining the maximum tolerated dose (MTD).
Detailed description
This pilot study will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal. Assessment of response will be confirmed by bone marrow studies performed at the end of cycles 2, 4, and 6 (each +/- 3 days).
Pharmacokinetics will be performed before and for up to 24 hours after drug administration on days 1 (for 24 hrs) and 15 (for 24 hrs) of cycle 1. Pharmacodynamic samples will be assessed pre-dosing on day 1 of cycle 1, pre-dosing on days 1 and 15 of cycle 2, and pre-dosing on day 15 of cycles 4 and 6.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IGF/MTX | Experimental | Drug: IGF/MTXThis arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
- Confirmed histologic diagnosis on bone marrow biopsy and aspirate within 28 days of trial entry prior to starting cycle 1.
- Platelets > 10 x 10^9/L
- ECOG performance status of 0, 1 or 2
- Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; prior use of systemic methotrexate > 1 month prior to study entry is allowed. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion.
Key exclusion criteria (13 listed)
- ECOG PS >2.
- Patients with active extramedullary disease.
- Pleural effusions or ascites.
- Active uncontrolled infection or severe systemic infection (enrollment is possible after control of infection).
- Myocardial infarction within ONE months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IGF/MTXAlso: insulin-like growth factor-1/methotrexate conjugate, 765IGF-methotrexate765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial | Drug | IGF/MTX |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events
Time frame: Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.
Number of Participants with Treatment-Emergent Adverse Events through study completion, up to a maximum duration of 10 28-day cycles.
11 secondary outcomes
Response Criteria for AML, Complete Remission (CR)
Time frame: Assessed after 2 cycles of 28 days each.
Response Criteria for AML, CR With Incomplete Recovery
Time frame: Assessed after 2 cycles of 28 days each.
Response Criteria for AML, Relapse.
Time frame: Assessed after 6 cycles of 28 days each.
Response Criteria for MDS, Complete Remission (CR)
Time frame: Assessed after 6 cycles of 28 days each.
Response Criteria for MDS, Marrow CR
Time frame: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Stable Disease
Time frame: Assessed after 6 cycles of 28 days each. Both patients had at least stable disease for at least 6 cycles.
Response Criteria for MDS, Failure
Time frame: Assessed after 6 cycles of 28 days each.
Response Criteria for MDS, Disease Progression, Blasts Measurements
Time frame: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Disease Progression, Hgb
Time frame: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Disease Progression, Neutrophils
Time frame: Assessed after 2 cycles of 28 days each.
Response Criteria for MDS, Survival, Death
Time frame: All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Myelodysplastic Syndromes
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mrinal S Patniak principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IGF/MTX in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by IGF Oncology, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (time frame: Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024.